Inhibition of human CYP2C9

Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of gamma-secretase modulators leading to highly efficacious agents for reduction of central nervous system Abeta(42) in various animal models. ..more

Title: Cyclic hydroxyamidines as amide isosteres: discovery of oxadiazolines and oxadiazines as potent and highly efficacious gamma-secretase modulators in vivo.

Abstract: Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of gamma-secretase modulators leading to highly efficacious agents for reduction of central nervous system Abeta(42) in various animal models. (PMID: 22098494)